The Guadalupe High School Association received a charter from the Texas legislature on December 3, 1849. William E. Jones, Andrew Neill, Thomas D. Johnson, H. C. Fountain, William H. Gordon, Samuel W. Elliott, and J. B. Morgan were among the trustees. A two-story building costing $5,000 was completed in 1850; W. J. Glass and Mary Hill taught 100 students during the first session in a building that became known as the Male Academy. A separate building for the girls' school was built in 1852 on land donated by William Tom. This building was destroyed by fire soon after it opened, but a new structure was completed by September 1853. Both academies ran five-month sessions.
In an effort to deal with financial difficulties, the association offered its facilities to the legislature as a possible site for Western University. The association then asked the legislature to give the school four leagues of public land. When these attempts failed, the stockholders held a fair to raise money but were unable to solve the association's financial problems. Several lawsuits against the association prompted the court to declared it insolvent. A group of citizens bought the properties for $3,800 at a sheriff's sale on January 2, 1855, and formed the Guadalupe Male and Female Academy. In 1858 the academy was transferred to the control of the Methodist Church, which ran the school until Civil War conditions forced it to close.